Conducting fibers

Cardiac muscle fibers come in two types: contractile fibers and conducting fibers. Contractile fibers contract. Conducting fibers do not contract but, like all muscle cells, conduct action potentials along the membrane. Conducting fibers act like neurons – they send action potentials a long distance (here on the order of centimeters) to communicate with other cells. Conducting fibers form gap junctions with other conducting fibers and also with contractile fibers. Contractile fibers also form gap junctions with other contractile fibers. This is how the signal to contract spreads through the heart: it starts with conducting fibers then spreads to contractile fibers then spreads to more contractile fibers. The set of conducting fibers is called the conduction system

The stimulus to contract starts with the specialized conducting fibers in the sinoatrial node (SA node). This stimulus spreads along the conduction system to atrial contractile fibers and further down the conduction system to ventricular contractile fibers. The heart beats with each action potential. Since the atrial contractile fibers receive the signal first, the atrium contracts first. The atria begin to relax by the time the ventricular contractile fibers get the signal.

The amazing thing about the conducting fibers is they have the property of autorhythmicity – they self-stimulate! As a consequence of this, the heart does not need and does not use external nerves to stimulate contraction. The heart beats on its own. The autonomic nerves that innervate the heart do not cause contraction but control the rate of contraction. Ugg, I really wanted to link to the transplant heart scene in the movie airplane but cannot find it.

To understand this, let’s review an action potential from a neuron or skeletal muscle

Action potential of skeletal muscle fiber/neuron

The plasma membrane maintains a resting potential when the cell is not excited (stimulated) of about -70 mV (milivolts). The cell has a threshold potential of about -55 mV; if the voltage of the membrane potential rises above this for any reason, the membrane will generate an action potential. When a neuron/skeletal muscle is stimulated, the membrane potential rises (depolarizes) slowly to threshold, and then. because voltage gated Na+ channels open at the threshold potential, the membrane depolarizes rapidly, then falls (repolarizes) rapidly and returns to the resting potential. The key - it takes some sort of external stimulus to get the membrane to rise to the threshold potential because the cell is able to maintain a resting potential.

Action potential in a conducting fiber

The key here is that conducting fibers are unable to hold or maintain a resting potential – there is constant leak of ions across the membrane that sloooowly depolarize the membrane. This slow rise in potential is called the prepotential and the current across the membrane that creates this is called the funny current. When threshold is reached, an action potential occurs.

Chronotropism – the regulation of HR

The action potential spreads throughout the heart to the contractile fibers and cause the fibers to contract, resulting in the heart beat. So for each action potential in a conducting fiber there is one heart beat. Autonomic neurons do not stimulate contraction but do control the rate of the ion leak causing the funny current, and so the duration of the prepotential. Paraympathetic innervation slows the leak and so increases the duration of the prepotential – this decreases heart rate (HR). Sympathetic innervation speeds up the leak and so decreases the duration of the prepotential – this increases heart rate (HR). The horomone epinephrine (also known as adrenaline) also does this. A pathologically low resting HR is called bradycardia. A pathologically high resting HR is called tachycardia. Endurance athletes have very low heart rates (many below 40 bpm) so ask a person with a low HR if they run or bike or row or ski before you call the emergency room.

The cardiac cycle

The cardiac cycle is roughly: 1) ventricles relax, 2) both atria contract, 3) atria relax and both ventricles contract. The diagram above breaks this down into five phases

Atrial contraction is atrial systole (“sis-toe-lee”). Atrial relaxation is atrial diastole (“die-ass-toe-lee”). Ventricular contraction is ventricular systole. Ventricular relaxation is ventricular diastole. When we just say “systole” we mean ventricular systole, for example systolic blood pressure is the blood pressure during ventricular systole.

You can memorize this (and quickly forget it) or you can understand it…

Pressure differences across the valve control if the valve is closed or open

Contraction of cardiac fibers increase blood pressure in the chamber and the difference in pressure between the atria, the ventricles, and the exit pipes (aorta/pulmonary trunk) determines valve state.

These principles in the context of the cardiac cycle

The best way to think about the events controlling the cardiac cycle

Cardiac performance

Cardiac output

cardiac output is the volume of blood ejected by the left ventricle per minute. A measure that is volume per time is flow. The units for the heart will be either L/min or mL/min.

Flow is a super important concept in understanding the heart, the blood vessels, and the lungs. The rate that an intertube floats down the saco river is a measure of speed. This is not flow. Flow is the volume of saco river water that passes a particular point over some time interval: stand by the river, start a stopwatch, measure the volume of water passing by you, stop the watch and stop measuring after 1 minute. How much has passed by you after 1 minute is the flow.

Cardiac output is

\[\begin{equation} CO = SV \times HR \end{equation}\]

where CO is cardiac output, SV is stroke volume, HR is heart rate. Some equations are not important to memorize. This one is. HR was mentioned earlier. The units of HR is beats/minute. Stroke volume is the volume of blood ejected by the left ventricle in one beat, so the units are mL/beat. So the units of CO are \(mL/minute = mL/beat \times beats/minute\). “beats” cancels.

How do we measure CO? We do this using volumes of the left ventricle at different points in the cardiac cycle

\[\begin{equation} SV = EDV - ESV \end{equation}\]

where EDV is end diastolic volume and ESV is end systolic volume. At the end of diastole, the left ventricle is filled (its at its maximum volume). At the end of systole, the ventricle has ejected its blood but there is still some remaining, this is ESV. So the amount ejected is

\[\begin{equation} Volume\;actually\;ejected (SV) = Volume\;available\;for\;ejection (EDV) - Volume\;remaining\;after\;ejection (ESV) \end{equation}\]

Note that \(\frac{SV}{EDV}\) is the ejection fraction

CO is increased by increasing preload – Frank-Starling law of the heart

preload is essentially a function of EDV. And, Frank-Starling is not one person but two. Remember the length-tension curve in skeletal muscle (thin-thick filament overap depends on the length of the sarcomere)? The same concept applies to cardiac muscle. What is interesting is that our heart tends to operate in the window of fiber lengths shorter than the length that generates maximum force (small pic in upper right above). Take a look at the graph above where we’ve zoomed into the working range of cardiac muscle fibers. Think of length as the starting length of the fiber (prior to shortening). The graph shows that the longer this starting length, the greater the force of contraction (tension).

Increased EDV increases the stretch on the ventricular wall (the extra blood pushes against the wall more and this **pressure expands the ventricle more – like blowing more air into a balloon) and this extra stretch extends the ventricular muscle fibers more prior to contraction. When the muscle contracts, the stretched fibers are closer to their optimum length and so they generate more force. And the increased contractile force increases the amount of blood ejected from the ventricles.

Increased EDV might occur because of a (1) higher volume of blood (common in endurance athletes) or (2) a slowdown of HR, allowing more time for filling (again, common in endurance athletes).

Increased preload increases SV so increases CO.

CO is increased by contractility

Contractility is the force generated by a cardiac muscle fiber at a specific fiber length. Essentially, this occurs because more Ca++ is in the cytoplasm and this increases the number of actin binding sites for myosin. The way to visualize contractility vs. preload is in the image above. Increased contractility increases SV so increases CO.

Afterload

Afterload is the arterial blood pressure that resists opening of the aortic valve. This pressure pushes on the valve, closing it. During isovolumetric contraction, pressure in the left ventricle is lower than that in the aorta but the ventricular pressure is rising sharply. When it rises above aortic pressure, the valve bursts open and blood is ejected. If aortic pressure is high (due to hypertension) then it takes longer for ventricular pressure to reach and surpass aortic pressure, so it takes longer for the valves to open. Since the length of ventricular systole is not a function of these pressures, if the duration of isovolumetric contraction increases then the duration of the ejection phase must decrease and less blood is ejected because there is less time to eject blood. So SV decreases and CO decreases.

Endogenous and exogenous agents that control CO

endogenous molecules are made in your body. exogenous molecules are made by another organism or a lab. epinephrine is endogenous. caffeine is exogenous. Increase in HR and/or SV increases CO. Decrease in HR and/or SV decreases CO. Low CO can result in brain dysfunction and kidney damage. Low CO due to low SV is congestive heart failure. Chronic high CO can cause kideny damage and hypertension, which can case all kinds of cardiovascular problems.

Chronotropic agents modulate HR. Inotropic agents modulate SV by their effect on contractility. Parasympathetic is negative inotropic. Sympathetic innervation and the hormone epinephrine (another name is adrenaline) are positive chronotropic and postive inotropic. Remember that the neurotransmitter of post-ganglionic sympathetic neurons is chiefly norepinphrine but a little epinephrine. beta adrenergic receptors are the epinephrine/norepinephrine recepters. beta-blockers inhibit these receptors and are negative chronotropic and negative inotropic. digitalis increases contractility and is positive inotropic.

Digitalis (digitoxin) is a metabolite in the common English cottage garden plant Digitalis purpurea (common name foxglove) which grows wild in Scotland (awesome!). The metabolite is extremely toxic to humans (and dogs and kids) because it inhibits the Na+/K+ pump. But, a tiny dose is too little to kill you but enough to increase contractility and has been a long-time treatment for congestive heart failure or dropsy (awesome!).